Epithalon (a.k.a. epithalone, epitalon) is a peptide hormone originally isolated from the pineal gland of cows. The four-amino-acid protein (Alanine-Glutamate-Asparagine-Glycine) has been found to have profound effects on telomere length, melatonin secretion, and immune system function. Current research into epithalon is investigating its ability to extend life, regulate sleep/wake cycles, and fight cancer.
In 2003, it was determined that epithalon could induce telomerase activity in human somatic cells grown in a laboratory setting1,2 . Telomeres are responsible for maintain the integrity of chromosomes (DNA strands) and telomerase is the enzyme responsible for maintaining telomere integrity. Without telomerase, telomeres slowly shorten over time. Once they become too short, apoptosis (programmed cell death) takes place and the cells with the shorted telomeres die. In certain cells, like reproductive cells, telomerase remains active forever. These cells are, in many respects, immortal. Somatic cells, however, do not have active telomerase and that means that they age and eventually die. The ability to reactivate telomerase in any somatic cell, let alone human somatic cells, suggests that epithalon might be able to ward off some of the effects of aging.
The exact mechanism by which epithalon leads to telomerase activation isn’t currently known. It is speculated that it can bind to promoter regions of the telomerase gene and directly activate transcription (conversion of DNA into RNA and RNA into the the protein enzyme)3 . In essence, the epithalon peptide is acting as a transcription factor 4 .
Pinealocytes, cells of the pineal gland, manufacture and release melatonin, which is a primary regulator of the sleep/wake cycle in diurnal organisms as well as a prominent hormone in seasonal reproductive cycles. Research on rat pinealocytes has shown that epithalon and other vilone peptides play an integral role in the synthesis and release of melatonin. They appear to act by stimulating an enzyme known as arylalkylamine-N-acetyltransferase (AANAT) along with the pCREB transcription protein5 .
AANAT is an enzyme that converts serotonin into melatonin. It is the next to last enzyme in the melatonin synthesis process and is functional in all vertebrate pineal glands. Activation of AANAT leads to the production of N-acetyl-serotonin, the penultimate molecule in the production of melatonin. In effect, AANAT primes the pump by producing more of the precursor to melatonin and thus preparing the pineal gland for adequate melatonin release.
pCREB is short for phosphorylated cAMP response element-binding protein. pCREB is a transcription factor, which means that it binds to DNA in order to increase or decrease the production of mRNA and protein from certain genes. pCREB plays an active role in the regulation of a number of genes that function in circadian rhythm and neurological modulation. Examples include somatostatin, VGF, corticotropin-releasing hormone, and PER1/PER2.
PER1 and PER2 are both important in the regulation of the circadian rhythm. PER1 is expressed in the suprachiasmatic nucleus of the hypothalamus, even during constant darkness, and thus regulates body’s the 24-hour cycle even in the absence of sunlight. PER2 is also expressed in the suprachiasmatic nucleus, but responds to light. It appears to help set the 24-hour clock, which PER1 maintains, to correspond with the day/light cycle. Interestingly, PER1 may play a critical role in the development of cancer and has been found to be under-expressed in cancer patients6 . By activating PER1, epithalon may help to ward off cancer development.
Research in birds has indicated the epithalon may play a role in regulating the function of the thymus7 . The thymus, located midway between the lungs, is the place where T-cells mature. T-cells are critical to adaptive immune function, the process by which the body adapts to foreign infections in order to better fight them off. Epithalon appears to promote the function of the thymus, helping it to remain healthy and to continue to produce functional T-cells. Normally, the thymus becomes dysfunction with age and adaptive immunity begins to fail. Studies in birds, however, indicate that epithalon can reverse the natural aging process in the thyms8 .
1. Khavinson, V. K., Bondarev, I. E. & Butyugov, A. A. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull. Exp. Biol. Med.135, 590-592 (2003).
2. Khavinson, V. K., Bondarev, I. E., Butyugov, A. A. & Smirnova, T. D. Peptide promotes overcoming of the division limit in human somatic cell. Bull. Exp. Biol. Med.137, 503-506 (2004).
3. Khavinson, V. K., Shataeva, L. K. & Chernova, A. A. Effect of regulatory peptides on gene transcription. Bull. Exp. Biol. Med.136, 288-290 (2003).
4. Khavinson, V., Shataeva, L. & Chernova, A. DNA double-helix binds regulatory peptides similarly to transcription factors. Neuro Endocrinol. Lett.26, 237-241 (2005).
5. Khavinson, V. K. et al. Molecular cellular mechanisms of peptide regulation of melatonin synthesis in pinealocyte culture. Bull. Exp. Biol. Med.153, 255-258 (2012).
6. Gery, S. et al. The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol. Cell22, 375-382 (2006).
7. Pateyk, A. V., Baranchugova, L. M., Rusaeva, N. S., Obydenko, V. I. & Kuznik, B. I. Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds. Bull. Exp. Biol. Med.154, 681-685 (2013).
8. Lin’kova, N. S., Kuznik, B. I. & Khavinson, V. K. [Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging]. Adv. Gerontol. Uspekhi Gerontol. Ross. Akad. Nauk Gerontol. Obshchestvo25, 478-482 (2012).